"neoBREASTIM": Atezolizumab Plus RP1 Oncolytic Immunotherapy in the NeoAdjuvant Setting of Triple-Negative Breast Cancer (neoBREASTIM)

"neoBREASTIM": A Phase 2 Study of Atezolizumab Plus RP1 Oncolytic Immunotherapy in the NeoAdjuvant Setting of Triple-Negative Breast Cancer (TNBC)

Neoadjuvant treatment is an important part of the treatment strategy for locally advanced TNBC having established a positive and significant correlation of pathologic Complete Response (pCR) with long-term clinical benefit such as Event-Free Survival (EFS) and Overall Survival (OS) as shown via large meta-analysis. Much effort has been made to identify novel agents and new drug combinations that can improve pCR rates in this specific clinical setting, which is the leading rationale to evaluate RP1 oncolytic immunotherapy in combination with Atezolizumab.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Combination product: Atezolizumab + RP1

Detailed Description

The combination of RP1 plus Atezolizumab, while being expected to result in increased efficacy, is not expected to result in significant additional toxicity, as compared to either agent alone. Capitalizing on the strong prognostic and predictive value of the TIL infiltrate in early-stage TNBC and the capacity of circulating tumor DeoxyriboNucleic Acid (ctDNA) detection to predict response to immunotherapy and NeoAdjuvant Chemotherapy (NAC), neoBREASTIM - a single-arm phase 2 study - will evaluate a novel, biomarker-driven combination of Atezolizumab plus RP1 oncolytic immunotherapy in the neo-adjuvant setting of patients diagnosed with early-stage, TIL-high TNBC.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75005
    • Institut Curie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female subject
2. Age ≥ 18 years old.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
4. Newly diagnosed Triple-Negative Breast Cancer (TNBC), defined as the absence of estrogen expression and progesterone expression, and of Human Epidermal growth factor Receptor 2 (HER2) overexpression, must be determined by local testing of a screening tumor sample as defined by American Society of Clinical Oncology/College of American Pathologists guidelines.
5. TNBC defined as the following combined primary tumor (T), regional lymph node (N), and metastatic (M) American Joint Committee on Cancer staging criteria: cT ≥15 - ≤30 mm, N0, M0 according to Mammogram, breast Ultrasound and MRI, and PET-CT. In case of a difference in the measurement of the primary tumor among different imaging methods, the breast MRI measurement is the reference.
6. Unicentric, unifocal and unilateral disease.
7. Tumor-infiltrating lymphocytes (TILs) ≥ 30%, as defined by the International TILs Working Group 2014.
8. ctDNA dosing at baseline.
9. Agreement to provide tissue samples (tumor biopsy at screening and on-treatment), and at surgery for immune monitoring and translational research activities.
10. Agreement to perform blood samples at screening, on-treatment, and at surgery for immune monitoring and translational research activities.

Exclusion Criteria:

1. Inflammatory breast cancer.
2. Prior treatment with an oncolytic virus-based therapy.
3. Patients with active significant herpetic infections or prior complications of Herpes Simplex Virus-1 (HSV-1) infection.
4. Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (e.g., acyclovir).
5. Diagnosis of immunodeficiency.
6. Has active autoimmune disease (e.g. inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, and multiple sclerosis, celiac disease, Wegener's granulomatosis) that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
7. Prior systemic immunosuppressive medication (except physiologic corticosteroid replacement therapy) within 30 days of planned start of study therapy.
8. Any live (attenuated) vaccine within 14 days of planned start of study therapy.
9. Prior immunotherapy, including tumor vaccine, cytokine, anti-CTLA4, PD-1/PD-L1 blockade or similar agents, T cell receptor-based (TCR-based) or Chimeric Antigen Receptor-T (CAR-T) cell based adoptive cell therapy.
10. Known history of, or any evidence of active, non-infectious pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Atezolizumab plus RP1 (Immulytic™) oncolytic immunotherapy; Atezolizumab IV q2w RP1 (Immulytic™) by imaging-guided intra-tumor (IT) route.

Combination product: Atezolizumab + RP1; Patients will be treated in a window period (ie 3 treatment cycles). After evaluation, patients that had no increase in ctDNA after 3 cycles (see Definition of ctDNA status) will continue on the same treatment (intratumoral injections of RP1 in combination with Atezolizumab) for a total of 10 treatment cycles prior to surgery.; Other Names: Tecentriq®; Vusolimogene Oderparepvec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the combination Atezolizumab plus RP1 oncolytic during the safety run-in phase	Incidence of combination Atezolizumab plus RP1 adverse events (AEs) graded according to NCI CTCAE v5.0 and nature and severity	9 months
Toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy during the safety run-in phase.	Dose Limiting Toxicity (DLT) during the first cycle of treatment of the combination Atezolizumab plus RP1 oncolytic immunotherapy	9 months
Residual Cancer Burden (RCB) 0-1 during the phase II part	Rate of RCB 0-1 at time of surgery (in patients with no increase in ctDNA after cycle 3)	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of RCB Score <= 1 at three cycles	Rate of RCB 0-1 after cycle 3 (in patients with no increase in ctDNA after cycle 3)	26 months
Safety and toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy	Incidence, nature and severity of adverse events (AEs) graded according to NCI CTCAE v5.0 from the treatment start to the surgery	60 months
Invasive disease-free survival (iDFS)	iDFS will be measured using regular follow-up visits	60 months
Percentage of TILs	The percentage of TILs will be estimated and compared between RCB rates 0-1 versus 2-3	30 months
Pre-treatment expression of Programmed Death-Ligand 1 (PD-L1)	Expression of PD-L1 will be estimated and compared between RCB rates 0-1 versus 2-3	30 months
Correlation between RCB rates and response by Positron Emission Tomography-Scan (PET-CT) or breast MRI	To correlate the response by RCB rates with response by PET-CT or breast MRI will be studied	60 months
RCB rates and response	To correlate the response by breast MRI with RCB 0-1 rates,	60 months
Breast Conservation Surgery (BCS)	The rate of Breast Conservation Surgery (BCS) will be presented	30 months
Correlation between RCB rates and radiomics analyses	To correlate the RCB rates with response by radiomics analyses.	30 months

Collaborators and Investigators

• Sponsor: Institut Curie
• Collaborators: Roche Pharma AG; Replimune Inc.
• Investigators: Study Director: Steven Le GOUILL, PhD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2024
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): May 7, 2025

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 6, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Triple Negative Breast Cancer; Oncolytic virus; Early-stage
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Atezolizumab
• Other Study ID Numbers: IC 2021-10; 2022-502311-12-00 (Registry Identifier: EU trial number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• IPD Sharing Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No